The objective of this work has been to understand the details of the interaction of self and foreign antigenic peptides with the MHC class I molecule by detailed kinetic and equilibrium binding methods. These studies permit us to understand the underlying biochemical rules that govern peptide/protein interactions, as well as how MHC molecules bind peptides both in intracellular compartments as well as the cell surface. In the past year we have further developed quantitative assays and have examined a number of peptide/MHC as well as several peptide antibody interactions. Understanding these processes on a biochemical and biophysical level provides a basis not only for understanding how MHC molecules bind and select self and antigenic peptides, but also offers an opportunity for rational design of peptide analogs for both immunization and for intervention in autoimmune disease.